Dramatic response of vemurafenib-induced cutaneous lesions upon switch to dual BRAF/MEK inhibition in a metastatic melanoma patient.

Détails

ID Serval
serval:BIB_FB42577CAC5A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Dramatic response of vemurafenib-induced cutaneous lesions upon switch to dual BRAF/MEK inhibition in a metastatic melanoma patient.
Périodique
Melanoma Research
Auteur(s)
Peters S., Bouchaab H., Zimmerman S., Bucher M., Gaide O., Letovanec I., Homicsko K., Michielin O.
ISSN
1473-5636 (Electronic)
ISSN-L
0960-8931
Statut éditorial
Publié
Date de publication
2014
Volume
24
Numéro
5
Pages
496-500
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish. pdf type: SHORT COMMUNICATIONS
Résumé
BRAF inhibitory therapy is the mainstream treatment for BRAF mutant advanced melanoma. However vemurafenib, a type I mutant BRAF V600 inhibitor, induces an array of proliferative skin disorders from keratosis pilaris-like and keratoacanthoma-like lesions to locally aggressive cutaneous squamous cell carcinoma (cuSCC). Dual BRAF/MEK inhibition is known to lower the incidence of such manifestations, but it is not known whether it can counteract established lesions. Here we show, for the first time, a dramatic response and a restitution ad integro upon dual inhibition of a widespread proliferative affection induced by BRAF monotherapy. A 75-year-old woman was diagnosed with a BRAF V600E mutated metastatic melanoma. Following dacarbazine (DTIC) and ipilimumab, the patient was started on 960 mg twice daily vemurafenib (Zelboraf), which resulted in complete response, but the patient also developed grade IV skin toxicity. Despite dose-reduction to 720 mg twice daily the side effects persisted. We hypothesized that a switch to double inhibition of the mitogen-activated protein kinase pathway with dabrafenib and trametinib could lead to improvement of the skin lesions, while preserving tumor control. The patient was closely followed for changes in skin lesions. We witnessed a rapid regression followed by complete disappearance of all side effects of vemurafenib except for grade I fatigue. The biopsied skin lesions show regression of established keratoacanthoma-like lesions with signs of apoptosis. Switching from the current standard of care vemurafenib therapy to the double BRAF/MEK inhibition in BRAF mutant melanoma patients results in rapid disappearance of established proliferative skin disorders.
Pubmed
Web of science
Création de la notice
08/09/2014 9:03
Dernière modification de la notice
20/08/2019 17:26
Données d'usage